Carcinogenesis, Vol 18, 1655-1658, Copyright © 1997 by Oxford University Press
KR Stayrook, JH McKinzie, YD Burke, YA Burke and PL Crowell
Perillyl alcohol has antitumor activity toward pancreas and other cancers
with low toxicity. Here, we have investigated the mechanism of action
responsible for the differential sensitivity of malignant versus
non-malignant pancreatic cells to the drug. We report that the rate of
apoptosis is over 6-fold higher in perillyl alcohol-treated pancreatic
adenocarcinoma cells than in untreated cells, and that the effect of
perillyl alcohol on pancreatic tumor cells is significantly greater than
its effect on non-malignant pancreatic ductal cells. Moreover, the perillyl
alcohol-induced increase in apoptosis in all of the pancreatic tumor cells
is associated with a 2- to 8-fold increase in the expression of the
proapoptotic protein Bak, but Bak expression is not affected by perillyl
alcohol in non-malignant cells. Thus, the antitumor activity of perillyl
alcohol toward pancreatic cancers may be due to preferential stimulation of
Bak-induced apoptosis in malignant versus normal cells. Bak may, therefore,
be a useful biomarker for the chemopreventive and therapeutic effects of
perillyl alcohol.
ARTICLES
Induction of the apoptosis-promoting protein Bak by perillyl alcohol in pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial cells
Department of Biology, Indiana University-Purdue University at Indianapolis, 46202, USA.
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